Biological differences between men and women contribute to many sex-specific illnesses and disorders.
Historically, it was argued that such differences were largely, if not exclusively, due to gonadal hormone
secretions. However, emerging research has shown that some differences are mediated by mechanisms
other than the action of these hormone secretions and in particular by products of genes located on
the X and Y chromosomes, which we refer to as direct genetic effects. This paper reviews the evidence
for direct genetic effects in behavioral and brain sex differences. We highlight the ‘four core genotypes’
model and sex differences in the midbrain dopaminergic system, specifically focusing on the role of
Sry. We also discuss novel research being done on unique populations including people attracted to
the same sex and people with a cross-gender identity. As science continues to advance our understanding
of biological sex differences, a new field is emerging that is aimed at better addressing the needs of both
sexes: gender-based biology and medicine. Ultimately, the study of the biological basis for sex differences
will improve healthcare for both men and women.